This Exploratory/Developmental Research Award will provide the funds for Drs. Nwogu and Pandey to study a novel Multifunctional Agent for image guided (PET/fluorescence) surgery and photodynamic therapy (PDT) in preclinical animal models. Translating this to the clinic will markedly change the treatment paradigm for locoregional non-small cell lung cancer and result in improved outcomes for patients. Detection of occult lymph node disease will be enhanced and intraoperative adjuvant photodynamic therapy can be accomplished. Additionally, patients whose comorbidities preclude surgical resection can have a repeatable, effective therapy (PDT). In order to achieve our imaging and therapeutic goals, this study is divided into following aims: 1) Compare the effectiveness of 124I-PS2 and 18F-Fluorodeoxyglucose (FDG) in imaging of lung tumors and lymph node metastases using an orthotopic lung cancer model in SCID mice. 2) Compare the effectiveness of photodynamic therapy using PS2 and Porfimer Sodium (Photofrin(R)) in human NSCLC xenografts established subcutaneously in SCID mice. On completion of the proposed project, we plan to study the therapeutic efficacy of this novel multifunctional radioisotope in a larger animal orthotopic lung cancer model such as dogs or pigs. PDT to both the lung tumor and its nodal drainage basin will be better refined in such larger animal models. This will be followed by phase I human clinical trials. The target subset of patients to whom this would be applicable include those with resectable primary NSCLC who are undergoing surgery to resect lesions that are larger than 3 cm or invading surrounding structures, or any patients with clinical ipsilateral thoracic lymph node disease. A local therapy to the regional lymph node basin and surgical margins that can be delivered with minimal morbidity immediately following resection of a primary tumor and its draining lymph nodes could dramatically reduce disease recurrence and improve long term survival. This is a novel therapeutic paradigm.